1. Field of the Invention
This invention relates to polymers of amino acids and methods for their preparation. More particularly, this invention pertains to water-insoluble and digestible polyamino acids, such as polymethionine, which are digestible by enzymes found in the human and animal digestive systems.
2. Description of the Prior Art
The amino acid fortification of foods will become very important in the future as larger amounts of vegetable proteins are used to replace or supplement less available and more costly protein from animal sources. Vegetable proteins, such as those contained in soy flour and wheat flour, are of lower nutritional quality than animal protein because they are limited in one or more of the essential amino acids, which include methionine, phenylanine, valine, leucine, isoleucine, lysine, threonine and tryptophan. These amino acids are absolutely required by humans and have to be obtained from dietary sources the same way as the vitamins. In addition, animal diets often benefit from amino acid fortification in order to produce healthier or larger animals. A comparison of the nutritional quality, measured in terms of a Protein Efficiency Ratio or PER value, for proteins from a variety of animal and vegetable sources is given in TABLE 1.
TABLE I ______________________________________ Comparison of Protein Nutritional Value Protein Efficiency Protein Source Ratio (PER)* ______________________________________ Egg white 3.8 Fish 3.0 Milk (whole) 2.8 Beef (dried) 2.8 Casein 2.5 Soy flour 1.9 Yeast 1.8 Wheat flour 1.2 Collagen (Gelatin) 0.1 ______________________________________ ##STR1##
Eggs, fish, meat and milk proteins have higher PER values and are of bette quality because they have a more complete complement of the essential amino acids. Proteins from the vegetable sources have much lower PER values because of limiting essential amino acid(s). The most serious problems occur with legumes (such as soybean), which are low in methionine, and with cereals, which are low in lysine. Yeasts and other single cell proteins have low PER values because they are also often limited in methionine.
One answer to the above problem is to directly fortify the vegetable proteins or yeast with the limiting amino acid(s). In certain cases this can be done, but unfortunately direct fortification with some amino acids, particularly methionine and lysine, causes significant problems. Some of the problems that occur are: toxicity of the free amino acid at higher concentrations; loss of nutritional value, due to reactivity of the free amino acid in the food system (Maillard reactions); loss of soluble amino acids, if cooking water is discarded; and taste and odor problems with the sulfur-containing amino acids (methionine).
Amino acid derivatives have been viewed as a possible way to supplement and avoid some of the problems associated with free amino acid addition. Methionine derivatives have been of particular interest because of their potential importance for supplementation of large amounts of soybean derived foods and feeds and because of more serious problems that occur with direct addition of the free amino acid.
For example, U.S. Ser. No. 3,952,115 (1976) to Damico et al. teaches the preparation of N-acyl-methionine esters and N-acyl derivatives of the sulfur amino acids for fortification of foodstuffs. U.S. Pat. No. 3,959,519 (1976) to Johnson teaches fortification of various foods with glycinemethionine dipeptides. U.S. Pat. No. 4,056,658 (1977) to Bertram et al. teaches the preparation and use of D,L-methionyl-D,L-methionine as a food and fodder additives. U.S. Pat. No. 4,024,286 (1977) to Cornelius et al. teaches the preparation of D,L-methionylglycine dipeptide and use as a food additive. None of these patents teach the synthesis of polymeric derivatives, however.
On the other hand, U.S. Pat. No. 2,650,214 (1953) to MacDonald teaches the preparation of synthetic alpha-monoaminomonocarboxylic acid polyamides, including the preparation of poly-D,L-methionine. These polymers were developed for their physical and structural characteristics, however, rather than for use as a nutritional food supplement, and therefore impliedly possess very high molecular weights.
More general information relating to the preparation of poly-alpha-amino acids can be found in Advances in Protein Chemistry, Vol. XIII, 1958, "Synthesis and Chemical Properties of Poly-Alpha-Amino Acids," pp. 244-475. The classical method for making these polymers is carried out by reacting the amino acid with phosgene in solvent such as benzene, dioxane, or ethyl acetate to produce the amino acid N-carboxy anhydride (NCA). The amino acid-NCA can be purified by recrystallization and is polymerized by dissolving it in an organic solvent such as dioxane with the addition of an initiator.
Aqueous polymerization of amino acid-NCAs is also reported for a number of amino acids, but no teachings are directed specifically to polymethionine, and nothing is suggested as to the significance of the degree of polymerization in regard to digestibility.
It is therefore an object of this invention to develop a form of polyamino acid, particularly a form of polymethionine, which is water-insoluble, completely digestible, non-toxic, non-reactive in food systems, and having less adverse taste or odor than the free amino acid.
This and other objects will become apparent from further reading of this specification.